High glucose induces adipogenic differentiation of muscle-derived stem cells

Abstract

Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ROS production and PKC␤ activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKC␤ siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously uncharacterized differentiation route triggered by high glucose that drives not only resident stem cells of the adipose tissue but also uncommitted precursors present in muscle cells to form adipose depots. This process may represent a feed-forward cycle between the regional increase in adiposity and insulin resistance that plays a key role in the pathogenesis of diabetes mellitus.adipocyte ͉ hyperglycemia ͉ PKC ͉ ROS

Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β

“…In this study they were compared in term of the effects on proliferation and differentiation of preadipocytes derived from both adipose tissue and mesenchymal stem cells. Following our previous study, 14 in which we showed that high glucose by means of PKC-b activation drove stem cells from both adipose tissue and skeletal muscle toward an adipogenic potential, in this study also we have blocked its activities in the presence of APDs, provided that is involved into the signals that underlie this process. In preadipocytes, the quetiapine, olanzapine and risperidone treatment induced an increase in both cell number (Figures 1b and c) and in adipose metabolism (detected with oil red staining and gene expression for glucose transporter-4 and lipoprotein lipase marker).…”

“…To this end, ADSCs, previously committed in mature adipocytes by culturing them in the presence of high glucose, 14 were treated for 3 days with different APDs (see Material and Methods section for details).…”

“…The MDSCs include the so-called satellite cells, that is, the precursor cells that are capable of differentiating in vivo to mature muscle fibers but that retain broad differentiation capacity, including the generation of adipocytes. 14 The effects of APDs on cellular proliferation, lipid production and gene expression were followed in both preadipocytes derived from ADSCs and in MDSC. As we have previously reported, 14 a high-glucose state drives stem cells from both adipose tissue and skeletal muscle toward an adipogenic potential, providing some insight into the signals that underlie this process.…”

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

“…[70][71][72][73] The predominant mechanism underlying the heightened oxidative stress in diabetes involves dysfunction of the mitochondrial electron transport system. 74 In hyperglycemic cells, more glucose becomes oxidized through the tricarboxylic acid (TCA) cycle, which results in an increased number of electron donors, NADH and FADH 2 , being fed into the electron transport chain.…”

Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements

“…Besides the excessive visceral deposition, several pathogenetic mechanisms are implicated, including brown to white fat transdifferentiation, mitochondrial damage and decreased mitochondrial biogenesis, an increased adipose cell size, a decreased insulin sensitivity of fat cells, and the failure of their storage function with the consequent peripheral lipotoxicity (Virtue & Vidal-Puig 2010), macrophage infiltration, and inflammation along with qualitative and/or quantitative changes in adipokine production (Vettor et al 2005), alteration in the angiogenetic process, and fibrosis development. Recently, stem cell abnormalities have also been described with alteration of the adipogenic process within adipose tissue or as an abnormal adipogenetic differentiation of stem cells residing in other organs (Aguiari et al 2008, Vettor et al 2009). The resulting metabolic consequences include abdominal obesity, insulin resistance, and atherogenic dyslipidemia along with a pro-thrombotic, inflammatory profile that defines the MetS.…”